Presbycusis - age-related hearing loss - is the primary communication disorder and one of the three top chronic medical conditions of our aged population. This program project consists of a set of discrete but connected disciplines organized to (1) investigate fundamental perceptual declines in presbycusis, and (2) to determine its neural and molecular bases. Discipline-oriented strategies are employed in a common set of specific aims building on key distinctions that have been discovered concerning the specialized roles of the ear and the brain and how they interact as one ages. We also focus on interactions observed among aging, disease/treatment states such as hormone imbalances, and their associated peripheral and central hearing deficits. Aging auditory deficits result in two main perceptual problems;loss in sensitivity biased toward the higher frequencies critical for understanding speech, and a serious reduction in sound processing capacity essential for understanding speech in background noise. Notably, we have demonstrated that temporal and spatial processing problems linked to speech perception-in-noise difficulties in the aged reside partly in auditory brainstem neural circuitry. The administrative, animal, and structure-function services cores will serve four multidisciplinary projects with experimental approaches ranging from audiology, speech perception, psychoacoustics, evoked potentials and psychophysics in humans, to startle reflex psychology, neurophysiology, evoked potentials, single-unit physiology, neuroanatomy, immunohistochemistry, and molecular biology in animals. Although translational interventions lie on the horizon, several additional aspects of the neural bases of age-related hearing loss must be investigated before they will be successful. In the next grant period, we propose a set of synergistically related human and animal experiments attacking these remaining issues to ensure eventual bench-to-bedside success: SPECIFIC AIM 1: Investigate Age-Related Changes in Spectro- Temporal Processing and Roles of lon Channels in these Changes. SPECIFIC AIM 2: Investigate Age- related Processing Declines for Competing Signals in Semi-Reverberant Listening Environments and the Underlying Neural Circuitry. SPECIFIC AIM 3: Investigate the Neural Bases and Possible Reversibility of the Accelerated Age-Related Hearing Loss Associated with Medical Conditions: Ear and Brain Analyses.